There is no specific treatment.[3] Rates of disease have been found to be about 30% among those with a history of multiple head injuries.[1] Population rates, however, are unclear.[2] Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "punch drunk syndrome".[1][3] Changing the rules in some sports has been discussed as a means of prevention.[1]

The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under one's own power for a short time and/or Parkinsonism, or tremors and lack of coordination. It can also cause speech problems and an unsteady gait. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.[7]

The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimer's disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.[8]

A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.[9]

Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.[11] A subtype of CTE is dementia pugilistica or boxer's dementia (from Latin pugilator - boxer) as it was initially found in those with a history of boxing, also called "punch-drunk syndrome".

Increased exposure to concussions and sub-concussive blows is regarded as the most important risk factor, which can depend on the total number of fights, number of knockout losses, the duration of career, fight frequency, age of retirement, and boxing style.[15]

Currently, CTE can only be definitively diagnosed by direct tissue examination after death, including full and immunohistochemical brain analyses.[16] Abnormal p-tau accumulation in "neurons, astrocytes, and cell processes in an irregular pattern at the depths of the cortical sulci" is the most specific feature of CTE and required for pathological diagnosis.[17][18]

The lack of distinct biomarkers is the reason CTE cannot typically be diagnosed while a person is alive. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be seen on routine neuroimaging tests such as CT or MRI.[19] Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are currently examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE.[5] Recently, more progress in in-vivo diagnostic techniques for CTE has been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.[9]

PET tracers that bind specifically to tau protein are desired to aid diagnosis of CTE in living individuals. One candidate is the tracer [18F]FDDNP, which is retained in the brain in individuals with a number of dementing disorders such as Alzheimer's disease, Down syndrome, progressive supranuclear palsy, familial frontotemporal dementia, and Creutzfeldt–Jakob disease.[20] In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains.[21] However, [18F]FDDNP binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were not consistent with the known neuropathology of CTE.[22] A more promising candidate is the tracer [18F]-T807, which binds only to tau. It is being tested in several clinical trials.[22]

A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain by means of a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught.[23] Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period of time between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may consist the earliest measurable event predicting CTE.[24]

Robert A. Stern, one of the scientists at the Boston University CTE Center,[25] said in 2015 that "he expected a test to be developed within a decade that will be able to diagnose C.T.E. in living people".[26]

Investigators have demonstrated that immobilizing the head during a blast exposure prevented the learning and memory deficits associated with CTE that occurred when the head was not immobilized. This research represents the first case series of postmortem brains from U.S. military personnel who were exposed to a blast and/or a concussive injury.[27]

Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport.[7] Medical professionals have called for such a ban since as early as the 1950s.[28]

Other individuals that have been diagnosed with CTE were involved in military service, had a previous history of chronic seizures, victims of domestic abuse, and or were involved in activities resulting in repetitive head collisions.[35]

The seminal work on the disease came from British neurologist Macdonald Critchley, who in 1949 wrote a paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers."[37] CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used.[38][39] In the early 2000s, Nigerian-American neuropathologist Bennet Omalu worked on the case of American football player Mike Webster, who died following unusual and unexplained behavior. In 2005 Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published his findings in the journal Neurosurgery in a paper which he titled "Chronic Traumatic Encephalopathy in a National Football League Player." This was followed by a paper on a second case in 2006 describing similar pathology.

In 2005 forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal Neurosurgery, based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.

In 2008, the CSTE at Boston University at the BU School of Medicine started the CSTE brain bank at the Bedford VA Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians[8] To date, the CSTE Brain Bank is the largest CTE tissue repository in the world.[9]
On December 21, 2009, the National Football League Players Association announced that it would collaborate with the CSTE at the Boston University School of Medicine to support the Center's study of repetitive brain trauma in athletes.[45] Additionally, in 2010 the National Football League gave the CSTE a $1 million gift with no strings attached.[46][47] In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to CSTE after their deaths.[40][48] In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the CSTE.[49] In 2010, 20 more NFL players and former players pledged to join the CSTE Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, Professional Wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the CSTE Brain Donation Registry consists of over 250 current and former athletes.[50] In 2011, former North Queensland Cowboys player Shaun Valentine became the first rugby player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film The Fighter, agreed to donate his brain upon his death.

In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimer's disease (AD)".[51]

In February 2011, Dave Duerson committed suicide,[52] leaving text messages to loved ones asking that his brain be donated to research for CTE.[53] The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duerson's was the first time he was aware of that such a request had been left by a suicide potentially linked to CTE.[54] Stern and his colleagues found high levels of the protein tau in Duerson's brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci,[8] are indicative of CTE.[55]

In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated. He is the second NHL player from the program at the Center for the Study of Traumatic Encephalopathy to be diagnosed with CTE postmortem.[56]

BUSM has also found indications of links between amyotrophic lateral sclerosis (ALS) and CTE in athletes who have participated in contact sports. Tissue for the study was donated by twelve athletes and their families to the CSTE Brain Bank at the Bedford, Massachusetts VA Medical Center.[57]